Abstract 2660: Plasminogen Activator Inhibitor 1 Gene Expression in Platelets is Significantly Correlated with Glucose and Lipid Metabolism and with Occurrence of Acute Coronary Syndrome
An elevated plasma level of plasminogen activator inhibitor-1 (PAI-1), which inhibits the fibrinolytic system, increases the risk of ischemic cardiovascular disease. Recent studies have demonstrated that PAI-1 in platelets affects thrombus formation; however, the precise pathophysiological role of PAI-1 in platelets remains to be elucidated. We sought to quantify the PAI-1 gene expression levels in the platelets of cardiovascular disease patients. We further sought to examine whether the PAI-1 gene expression level in the platelets is a prognostic marker for reattacks of cardiovascular events. We measured PAI-1 gene expression levels in the platelets, using real time RT-PCR in 107 consecutive patients: 39 patients with acute coronary syndrome (ACS Group); 35 patients with stable exertional angina (SEA Group); and, 33 control subjects (Control Group). The PAI-1 mRNA levels in the platelets were significantly higher in the ACS Group (1.42 [0.79 to 5.71]) than in either the SEA Group (1.05 [0.38 to 1.96]) or the Control Group (0.59 [0.30 to 1.08]) (p<0.01). The platelet PAI-1 mRNA levels were significantly correlated with HbA1c and with fasting plasma glucose levels (p<0.03). The platelet PAI-1 mRNA levels were significantly inversely correlated with high density lipoprotein-cholesterol levels (p<0.03). In the ACS Group, 5 reattacks of cardiovascular events occurred during hospitalization (2 CABGs due to unstable angina; 2 cerebral infarctions; and, 1 cardiac sudden death). The platelet PAI-1 mRNA levels were significantly higher in the patients with reattacks of cardiovascular events (7.88 [2.91 to 17.43]) than in those without reattacks (1.40 [0.74 to 5.01]) (p<0.05). Multiple logistic regression analysis revealed that a high PAI-1 mRNA level in the platelets was the single most predictive independent risk factor for a reattack of a cardiovascular event during hospitalization. The platelet PAI-1 gene expression levels were specifically elevated in patients with ACS, especially in those with abnormal glucose and/or lipid metabolism; furthermore, a high PAI-1 gene expression level in the platelets significantly increased the risk of short term adverse outcomes in patients with ACS.